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Cell Stem Cell 10:273283 Bernet JD, Doles JD, Hall JK, Kelly Tanaka K, Carter TA, Olwin BB (2014) p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice

This process is achieved by regulating the expression levels of -catenin and its downstream targets, including CyclinD1, MMP7, c-Myc, c-Jun, AXIN2 and glutamine synthase [61]

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We identified glutathione metabolism as a prominent rhythmic pathway linking microbial rhythmicity to host inflammatory oscillations.Citation 61 This interpretation is consistent with previous studies showing that glutathione levels, GCL activity, and Gclc-related biosynthetic programs exhibit circadian variation and are under clock-dependent regulation.Citation 62 Integrated multi-omics analyzes combining transcriptomic and metabolomic profiling revealed that glutathione metabolic oscillations were preserved in LFD and HFD-FOS groups but absent in HFD-fed mice, with the glutamate-cysteine ligase catalytic subunit ( Gclc ) displaying particularly robust circadian expression patterns that correlated with microbial diurnal dynamics.Citation 63 , Citation 64 These oscillations encompassed both glutathione synthesis and regeneration, forming a coherent metabolic rhythm aligned with microbial ecological shifts.Citation 65 Functional validation through colon-specific Gclc knockdown showed that glutathione synthesis is functionally required for maintaining inflammatory rhythms, as its inhibition markedly dampened rhythmic amplitude and abolished the restorative effects of microbial rhythmicity